Seroatlas · Human Serome Atlas

PKP4

Plakophilin-4

Also known as: p0071, PKP4_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q99569
Gene: PKP4
Ensembl: ENSG00000144283
Chromosome: 2
Canonical length: 1192 aa
Protein class: Plasma proteins, Predicted intracellular proteins
Subcellular location: Plasma membrane,Cell Junctions

OverviewNCBI Gene

Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

Canonical amino-acid sequenceUniProt

1192 residues, UniProt reviewed canonical sequence.

>Q99569|PKP4
     1  MPAPEQASLV EEGQPQTRQE AASTGPGMEP ETTATTILAS VKEQELQFQR LTRELEVERQ
    61  IVASQLERCR LGAESPSIAS TSSTEKSFPW RSTDVPNTGV SKPRVSDAVQ PNNYLIRTEP
   121  EQGTLYSPEQ TSLHESEGSL GNSRSSTQMN SYSDSGYQEA GSFHNSQNVS KADNRQQHSF
   181  IGSTNNHVVR NSRAEGQTLV QPSVANRAMR RVSSVPSRAQ SPSYVISTGV SPSRGSLRTS
   241  LGSGFGSPSV TDPRPLNPSA YSSTTLPAAR AASPYSQRPA SPTAIRRIGS VTSRQTSNPN
   301  GPTPQYQTTA RVGSPLTLTD AQTRVASPSQ GQVGSSSPKR SGMTAVPQHL GPSLQRTVHD
   361  MEQFGQQQYD IYERMVPPRP DSLTGLRSSY ASQHSQLGQD LRSAVSPDLH ITPIYEGRTY
   421  YSPVYRSPNH GTVELQGSQT ALYRTGSVGI GNLQRTSSQR STLTYQRNNY ALNTTATYAE
   481  PYRPIQYRVQ ECNYNRLQHA VPADDGTTRS PSIDSIQKDP REFAWRDPEL PEVIHMLQHQ
   541  FPSVQANAAA YLQHLCFGDN KVKMEVCRLG GIKHLVDLLD HRVLEVQKNA CGALRNLVFG
   601  KSTDENKIAM KNVGGIPALL RLLRKSIDAE VRELVTGVLW NLSSCDAVKM TIIRDALSTL
   661  TNTVIVPHSG WNNSSFDDDH KIKFQTSLVL RNTTGCLRNL SSAGEEARKQ MRSCEGLVDS
   721  LLYVIHTCVN TSDYDSKTVE NCVCTLRNLS YRLELEVPQA RLLGLNELDD LLGKESPSKD
   781  SEPSCWGKKK KKKKRTPQED QWDGVGPIPG LSKSPKGVEM LWHPSVVKPY LTLLAESSNP
   841  ATLEGSAGSL QNLSAGNWKF AAYIRAAVRK EKGLPILVEL LRMDNDRVVS SVATALRNMA
   901  LDVRNKELIG KYAMRDLVNR LPGGNGPSVL SDETMAAICC ALHEVTSKNM ENAKALADSG
   961  GIEKLVNITK GRGDRSSLKV VKAAAQVLNT LWQYRDLRSI YKKDGWNQNH FITPVSTLER
  1021  DRFKSHPSLS TTNQQMSPII QSVGSTSSSP ALLGIRDPRS EYDRTQPPMQ YYNSQGDATH
  1081  KGLYPGSSKP SPIYISSYSS PAREQNRRLQ HQQLYYSQDD SNRKNFDAYR LYLQSPHSYE
  1141  DPYFDDRVHF PASTDYSTQY GLKSTTNYVD FYSTKRPSYR AEQYPGSPDS WV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PKP4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.48
Highest tissue expression: 336 nTPM

Expression across tissuesHPA

Tissue

spinal cord: 336 nTPM
midbrain: 186 nTPM
hippocampal formation: 118 nTPM
basal ganglia: 105 nTPM
amygdala: 103 nTPM
hypothalamus: 83 nTPM

Single-cell type

distal convoluted tubule cells: 1,481 nCPM
oligodendrocytes: 1,268 nCPM
loop of henle epithelial cells: 1,143 nCPM
proximal tubule cells: 714 nCPM
vascular endothelial cells: 654 nCPM
lacrimal acinar cells: 593 nCPM

Immune cell

non-classical monocyte: 2 nTPM
T-reg: 0.7 nTPM
memory CD4 T-cell: 0.5 nTPM
naive CD4 T-cell: 0.4 nTPM
classical monocyte: 0.3 nTPM
MAIT T-cell: 0.2 nTPM

Brain region

medulla oblongata: 367 nTPM
white matter: 324 nTPM
spinal cord: 308 nTPM
basal ganglia: 306 nTPM
midbrain: 282 nTPM
pons: 274 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.64
gnomAD pLI: 0
gnomAD missense Z: 0.97
DepMap mean gene effect: 0.05
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

cadherin binding

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of PKP4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PKP4 as an antibody target. Whether an autoantibody or antibody against PKP4 could matter depends on whether native PKP4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PKP4 is annotated at the cell surface, where native PKP4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label PKP4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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